Cryptorchidism Optimal Cutoff Value of Contralateral Testicular Size for Prediction of Absent Testis in Japanese Boys With Nonpalpable Testis Yasuhiro Shibata, Yoshiyuki Kojima, Kentaro Mizuno, Akihiro Nakane, Toshiki Kato, Hideyuki Kamisawa, Kenjiro Kohri, and Yutaro Hayashi OBJECTIVES
METHODS
RESULTS
CONCLUSIONS
To investigate the accuracy of contralateral testicular hypertrophy in Japanese boys with a nonpalpable testis and to determine the optimal cutoff value of the contralateral testicular size to predict the absence of the testis. From December 2003 to November 2009, we evaluated 55 boys ⬍60 months old (mean age 19.4) with a unilateral nonpalpable testis and compared their findings with those of a control group. The control group included 20 age-matched boys with 40 testes. The nonpalpable status of the testes was diagnosed by physical examination, and the contralateral testis was measured with calipers before surgery. A sensitivity and specificity analysis were performed using computer software. At surgery, the testis was found in 22 of the 55 boys and was absent in 33. Of the 33 boys with an absent testis, 4 had a blind-ending vessel and 29 had an atrophic cord and testicular nubbin in the canal or scrotum. The mean contralateral testicular length and volume in the boys with an absent testis was 22.4 mm and 2.20 cm3 compared with 16.6 mm and 1.10 cm3 in the boys with the testis present and 16.6 mm and 1.18 cm3 in the controls, respectively (P ⬍ .01). The predictive accuracy, sensitivity, and specificity for an absent testis was 87.3%, 81.8%, and 95.5% for the length and 85.5%, 84.8%, and 86.4% for the volume, respectively, at the optimal cutoff value of 21 mm in length and 1.6 cm3 in volume. Our data have shown that contralateral testicular hypertrophy strongly indicates an absent testis in Japanese boys. The optimal cutoff for contralateral testicular hypertrophy with calipers was 21 mm and 1.6 cm3. This result has provided valuable information for preoperative counseling and treatment planning. UROLOGY 76: 78 – 81, 2010. © 2010 Elsevier Inc.
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our possible conditions exist in boys with a unilateral nonpalpable testis: an intra-abdominal testis, an extra-abdominal testis, an intra-abdominal vanishing testis, and an extra-abdominal testicular nubbin. It is important to diagnose each condition with accuracy and choose the subsequent appropriate treatment according to the diagnosis. Laparoscopy has been found to be the most useful for the diagnosis of a nonpalpable testis. However, the preoperative prediction before the surgical procedure can sometimes allows one to plan for all possible contingencies that could be encountered.1 Although multiple imaging approaches exist for the preop-
From the Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Reprint requests: Yutaro Hayashi, M.D., Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 Japan. E-mail:
[email protected] Submitted: December 6, 2009; received (with revisions): February 15, 2010
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erative evaluation of the nonpalpable testis,1,2 the cost and need for general anesthesia can limit their use. Testicular development can be affected by various factors, including genetic, hormonal, and environmental conditions. In boys with a nonpalpable testis, a contralateral testis has been reported to be affected by the condition of the nonpalpable testis, whether absent or present. Some studies have reported that the presence of contralateral testicular hypertrophy strongly indicates an absent testis on the nonpalpable side.3-8 These findings of contralateral testicular hypertrophy can provide useful information for the diagnosis and preoperative counseling and treatment planning, in addition to imaging studies. It has been reported that testes are larger in the white than in the Asian populations.9-11 To our knowledge, ethnic differences in contralateral testicular hypertrophy in the absent testis has not been previously reported. Previous reports of contralateral testicular hypertrophy have been from the United States and Europe. No report 0090-4295/10/$34.00 doi:10.1016/j.urology.2010.02.043
has been published on contralateral testicular hypertrophy in Japanese boys with an absent testis. In the present study, therefore, we investigated the accuracy of contralateral testicular hypertrophy and determined the optimal cutoff value to predict the presence or absence of a nonpalpable testis in Japanese boys.
MATERIAL AND METHODS From December 2003 to November 2009, we evaluated 55 Japanese boys ⬍60 months old with a unilateral nonpalpable testis at a single institution. The age of the 55 boys was 8-46 months old (mean 19.4) at surgery. A nonpalpable testis was found on the left side in 43 boys. None had previously received human chorionic gonadotropin therapy. The testis was found in 22 (40%) of the 55 boys at surgery. Nineteen testes were intra-abdominal undescended testes, including 3 “peeping” testes, and 3 testes were intracanalicular undescended testes. In our study we defined “peeping” testes as the testes which are located around the internal inguinal ring and are moving easily between the canal and the abdominal cavity. The testis was absent (monorchia) in 33 patients (60.0%); 4 had a blind ending vessel, 2 had an atrophic cord, and 27 had a testicular nubbin in the canal or scrotum. To prevent missing the intra-abdominal testes, we confirmed the presence of the blind ending vessel or testicular nubbin in all cases by inguinal exploration and laparoscopic surgery. In the 33 cases of an absent testis, the testicular nubbin was palpable in 11 patients in the scrotum and in 3 patients in the groin at clinical examination and was confirmed at surgery. The nonpalpable status was diagnosed by physical examination, and the contralateral testicular size was measured with calipers before surgery. To avoid the bias against diagnostic imaging, the nonpalpable status of the testis was diagnosed before any diagnostic imaging was done. The length of the major axis of the contralateral testis was adopted as the testicular size in the present study. Patients with a unilateral nonpalpable testis were divided into 2 groups, those with an undescended testis (group 1; n ⫽ 22) and those with monorchia (group 2; n ⫽ 33), according to the surgical outcome. In the present study, we defined an undescended testis as one that was present intracanalicularly or intra-abdominally and monorchia as an absent testis, including testicular agenesis or a vanishing testis, with or without a testicular nubbin. The contralateral testicular size of the 2 groups with a nonpalpable testis was compared with the testicular size of the control group (group 3). The control testicular size was measured in age-matched 40 testes in 20 Japanese boys with no testicular abnormalities. The age of the boys in group 3 was 4 to 47 months (mean 19.4). A contralateral testicular size greater than the cutoff was tested as a positive predictive factor for an absent nonpalpable testis. When a nonpalpable testis was absent, the test was regarded as a positive result. When a testis was present, the test was scored as a false-positive result. The histologic features were analyzed and compared with the contralateral testicular conditions. The data are presented as the mean ⫾ standard deviation. Analyses were performed using the computer software Statcel (Yodosya, Tokyo, Japan). Bonferroni’s test was performed to determine whether the group with an absent testis had a larger contralateral testis than the control group. Fisher’s exact test UROLOGY 76 (1), 2010
Table 1. Distribution of control and contralateral testicular size Contralateral Testicular Size Length (mm) ⱖ22 21 20 19 18 ⱕ17 Total Volume (cm3) ⱖ2.0 1.8-2.0 1.6-1.8 1.4-1.6 1.2-1.4 ⱕ1.2 Total
Testis (n) Testis Present Testis Absent Control (Group 1) (Group 2) (Group 3) 1 0 3 2 2 14 22
23 4 2 3 1 33
3 3 7 17 40
1 1 1 4 2 13 22
17 3 8 2 0 3 33
4 2 5 7 22 40
Table 2. Comparison of average control and contralateral testicular size Testicular Condition Contralateral Testicular Size
Testis Present (Group 1)
Testis Absent (Group 2)
Control (Group 3)
Length (mm) 16.6 ⫾ 2.8 22.4 ⫾ 2.6* 16.6 ⫾ 2.0 Volume 1.10 ⫾ 0.39 2.20 ⫾ 0.75* 1.18 ⫾ 0.39 (cm3) * P ⬍ .01 compared with control and testis present.
was performed to demonstrate the relationship between the absent testis and contralateral testicular hypertrophy. A sensitivity and specificity analysis was done to determine the cutoff value for an enlarged contralateral testis. The results were considered statistically significant at P ⬍.05.
RESULTS The distribution of the contralateral testicular size in each group is listed in Table 1. In groups 1 and 3, 21 (95.5%) of 22 testes and 40 (100%) of 40 testes were ⱕ20 mm, respectively. In contrast, 27 (81.8%) of 33 testes were ⬎20 mm in group 2. The mean size of the contralateral testes is listed in Table 2. The contralateral testicular size in group 2 was 22.4 ⫾ 2.6 mm or 2.20 ⫾ 0.75 cm3 and was significantly larger than that of group 1 (16.6 ⫾ 2.8 mm or 1.10 ⫾ 0.39 cm3) and group 3 (16.6 ⫾ 2.0 mm or 1.18 ⫾ 0.39 cm3). No significant difference was found in the testicular size between groups 1 and group 3. Figure 1 shows the results of the sensitivity and specificity analysis. The curves of sensitivity, which represents the percentage of patients with an absent testis that was predicted to be absent, and specificity, considered the percentage of patients with a testis detected that was predicted to be present, crossed at a length of 20-21 mm and a volume of 79
Figure 1. Sensitivity and specificity analysis. Curves crossed at (A) length of 20-21 mm and (B) volume of 1.6 cm3. At this cutoff of 21 mm or 1.6 cm3, prediction accuracy was greatest at 87.3% and 85.5%, respectively.
1.6 cm3. At this cutoff of 21 mm or 1.6 cm3, the prediction accuracy was greatest and the percentage of the prediction accuracy was 87.3% for the length and 85.5% for the volume. Fisher’s exact testing of the data listed in Table 1 using these cutoff values indicated a statistically significant relationship between an absent testis and contralateral testicular hypertrophy in length or volume (odds ratio 94.5 or 35.5, P ⫽ .00000002 or P ⫽ .0000002, respectively). The sensitivity, specificity, positive predictive value, and negative predictive value was 81.8%, 95.5%, 96.4%, and 77.8% for the length cutoff and 84.8%, 86.4%, 90.3%, and 79.1% for the volume cutoff, respectively. Inguinal incision was done in 29 boys with preparation for transinguinal laparoscopy. Transinguinal laparoscopy was done in cases in which the testis, vas, or vessels could not be identified.12,13 With inguinal incision, testes were found in 9 of 29 patients, and 7 had testes intra-abdominally and 2 in the canal. Standard orchiopexy was done in the 2 cases of an intra-abdominal testis and 2 cases of an intracanalicular testis. Division of the spermatic vessels as a 1-stage procedure was done in 3 patients, and the Jones method was done in 2. The remaining 20 of 29 patients had an absent testis. Of these 20 patients, a testicular nubbin was found in 17 and a blind ending vessel in the canal was found in 3. Conventional subumbilical laparoscopic surgery was done in the latest 26 patients.14 In 13 cases, a testis was found, and laparoscopic orchiopexy was performed. Of 80
these, 12 were intra-abdominal and 1 was intracanalicular. In the remaining 13 cases of an unidentified testis, atrophic cords were investigated in the internal ring, the end of the atrophic cord was confirmed, and all were removed.
COMMENT In the present study, we investigated the accuracy of contralateral testicular hypertrophy in Japanese boys with a nonpalpable testis. We determined the optimal cutoff value to predict the presence or absence of a nonpalpable testis. To determine whether a nonpalpable testis is present or absent, physical examination, as well as, sometimes, diagnostic imaging such as ultrasonography and magnetic resonance imaging, is used. Although the diagnostic accuracy of these imaging studies has been improving, it is still difficult to determine whether a testis is present or absent.2,15-17 Compensatory contralateral testicular hypertrophy is a common clinical finding in boys with an absent testis and gives supplementary information for predicting the condition of the nonpalpable testis. In the present study, although the contralateral testicular size of the present testis was similar to the average descended testicular size, the contralateral testicular size of the absent testis was significantly larger than the contralateral testicular size of those with a testis present and the average descended testicular size. Thus, contralateral testicular hypertrophy UROLOGY 76 (1), 2010
occurs in boys with an absent testis but does not occur in boys with a testis present. Previous studies revealed a clinical cutoff value of compensatory testicular hypertrophy in the United States and Europe.3-5 Laron et al3 first described compensatory testicular hypertrophy. However, their series included prepubertal, pubertal, and postpubertal patients with palpable and nonpalpable undescended testes.3 Koff4 reported 12 of 37 boys with an absent testis, and all these boys had contralateral testicular hypertrophy ⬎2 cm or ⬎2 cm3. In addition, Hurwitz and Kaptein5 reported that testicular hypertrophy of ⱖ1.8 cm predicted an absent testis. However, these reports did not provide the ethnic backgrounds of the patients, although it is also known that racial variation exists in testicular size.9-12 The testicular weight of Asian men was lower than that of white men at autopsy.9 Johnson et al11 reported ethnic differences in testicular structure and the response to hormonal stimulation and that the mean testicular weight or volume of autopsied Asian men was lower than that of white and Hispanic men. Therefore, we considered that the optimal cutoff value of the contralateral testis in Japanese boys with a nonpalpable testis to predict the presence or absence of testis was needed. In the present study, we demonstrated an optimal cutoff value for Japanese boys with an absent testis. The optimal cutoff for contralateral testicular hypertrophy with calipers was 21 mm or 1.6 cm3, comparable to the cutoff of previous reports from Western countries. This suggests that in contrast to the presence of ethnic differences in testicular size in adults, contralateral testicular conditions in Japanese boys with an absent testis is similar to that in boys from the United States and Europe. This is the first report to show the optimal cutoff value of contralateral testicular size for the prediction of an absent testis in Japanese boys with a nonpalpable testis.
CONCLUSIONS Our data have shown that contralateral testicular hypertrophy in boys who have a nonpalpable testis strongly indicates an absent testis in Japanese boys. The optimal cutoff value for contralateral testicular hypertrophy with calipers was 21 mm or 1.6 cm3. These results have pro-
UROLOGY 76 (1), 2010
vided valuable information for preoperative counseling and treatment planning for a nonpalpable testis. References 1. Franco I. Evaluation and management of impalpable testes. In: Belman AB, King LR, Kramer S, eds. Clinical Pediatric Urology, 2nd ed. London: Martin Dunitz; 2002:1155-1172. 2. Siemer S, Humke U, Uder M, et al. Diagnosis of nonpalpable testes in childhood: comparison of magnetic resonance imaging and laparoscopy in a prospective study. Eur J Pediatr Surg. 2000;10:114-118. 3. Laron Z, Dickerman Z, Ritterman I, et al. Follow-up of boys with unilateral compensatory testicular hypertrophy. Fertil Steril. 1980; 33:297-301. 4. Koff SA. Does compensatory testicular enlargement predict monorchism? J Urol. 1991;146:632-633. 5. Hurwitz RS, Kaptein JS. How well does contralateral testis hypertrophy predict the absence of the nonpalpable testis? J Urol. 2001; 165:588-592. 6. Huff DS, Snyder HM III, Hadziselimovic F, et al. An absent testis is associated with contralateral testicular hypertrophy. J Urol. 1992; 148:627-628. 7. Mesrobian HG, Chassaignac JM, Laud PW. The presence or absence of an nonpalpable testis can be predicted from clinical observations alone. BJU Int. 2002;90:97-99. 8. Belman AB, Rushton HG. Is an empty left hemiscrotum and hypertrophied right descended testis predictive of perinatal torsion? J Urol. 2003;170:1674-1675. 9. Diamond JM. Ethnic differences: variation in human testis size. Nature. 1986;320:488-489. 10. Mittwoch U. Ethnic differences in testis size: a possible link with the cytogenetics of true hermaphroditism. Hum Reprod. 1988;3:445-449. 11. Johnson L, Barnard JJ, Rodriguez L, et al. Ethnic differences in testicular structure and spermatogenic potential may predispose testes of Asian men to a heightened sensitivity to steroidal contraceptives. J Androl. 1998;19:348-357. 12. Kanemoto K, Hayashi Y, Kojima Y, et al. The management of nonpalpable testis with combined groin exploration and subsequent transinguinal laparoscopy. J Urol. 2002;167:674-676. 13. Hayashi Y, Mogami T, Sasaki S, et al. Transinguinal laparoscopy for nonpalpable testis. Int J Urol. 1996;3:274-277. 14. Kojima Y, Mizuno K, Imura M, et al. Laparoscopic orchiectomy and subsequent internal ring closure for extra-abdominal testicular nubbin in children. Urology. 2009;73:515-519. 15. Nijs SM, Eijsbouts SW, Madern GC, et al. Nonpalpable testes: is there a relationship between ultrasonographic and operative findings? Pediatr Radiol. 2007;37:374-379. 16. Elder JS. Ultrasonography is unnecessary in evaluating boys with a nonpalpable testis. Pediatrics. 2002;110:748-751. 17. Maghnie M, Vanzulli A, Paesano P, et al. The accuracy of magnetic resonance imaging and ultrasonography compared with surgical findings in the localization of the undescended testis. Arch Pediatr Adolesc Med. 1994;148:699-703.
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